Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons

Lundström, Annika; Gallio, Marco; Englund, Camilla; Steneberg, Pär; Hemphälä, Johanna; Aspenström, Pontus; Keleman, Krystyna; Falileeva, Ludmilla; Dickson, Barry J.; Samakovlis, Christos

doi:10.1101/gad.310204

Cited by 106 publications

(107 citation statements)

References 54 publications

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“…Slit stimulation leads to recruitment of a Dock and Pak complex to the Robo receptor and increases Rac activation (Fan et al, 2003). In contrast, Vilse, a conserved family of RhoGAPs, regulate the repellent response to Slit by binding to the intracellular domain of Robo receptors and promoting Rac inactivation (Lundstrom et al, 2004). Our results are indicative of an inhibitory, and not a directional, effect of Slit2 on medulloblastoma cells.…”

Section: Discussionmentioning

confidence: 68%

“…Cdc42 and Rac1 play roles in Slit-mediated repulsion (Wong et al, 2001;Fan et al, 2003;Lundstrom et al, 2004). To assess Rho-GTPase activation by Slit2, medulloblastoma and glioma cells were cultured in medium conditioned by HEK or Slit2 cells and pulldown assays of activated Cdc42, Rac1 and RhoA were conducted.…”

Section: Slit2 Downregulates Activated Cdc42 In Medulloblastoma Cellsmentioning

confidence: 99%

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Inhibition of medulloblastoma cell invasion by Slit

et al. 2006

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Section: Discussionmentioning

confidence: 68%

Section: Slit2 Downregulates Activated Cdc42 In Medulloblastoma Cellsmentioning

confidence: 99%

Inhibition of medulloblastoma cell invasion by Slit

et al. 2006

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“…Although both of our studies point to a role of CrGAP͞ Vilse in Robo signaling, it appears that the exact mechanism might differ in midline neurons versus in trachea. Overexpression of Vilse in the trachea of robo mutants ameliorates the phenotypes of robo (17); in contrast, overexpression of CrGAP͞ Vilse in midline axons exacerbates the robo phenotype (this study). This intriguing difference calls for further investigation of how precisely Robo activation regulates CrGAP function in neurons.…”

Section: Discussionmentioning

confidence: 78%

“…During the preparation of our manuscript, CrGAP was independently discovered as a mediator of Robo repulsion in tracheal cells and axons, and was named Vilse (17). Intriguingly, our studies revealed that CrGAP͞Vilse may function differently during signaling downstream of Robo in midline neurons versus tracheal cells.…”

mentioning

confidence: 88%

Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion

Labrador

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The regulators of the Rho-family GTPases, GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs), play important roles in axon guidance. By means of a functional genomic study of the Rho-family GEFs and GAPs in Drosophila, we have identified a Rho-family GAP, CrossGAP (CrGAP), which is involved in Roundabout ( axon guidance ͉ GTPase-activating protein ͉ guanine nucleotide exchange factor ͉ Slit ͉ Roundabout

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“…In the developing vasculature, important roles have been attributed to SemaphorinNeuropilin/Plexin, Netrin-Unc5B and Slit-Robo4 signalling (Lu et al, 2004;Kamei and Weinstein, 2005;Suchting et al, 2006). Similarly, Robo signalling has been involved in tracheal pathfinding in the developing nerve cord in Drosophila (Lundstrom et al, 2004). Do stalk cells of endothelial sprouts and tracheal branches also show similar cellular behaviour?…”

Section: Do General Cellular Principles Underlie Branching Morphogenementioning

confidence: 99%

Tracheal branching morphogenesis inDrosophila: new insights into cell behaviour and organ architecture

2008

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2055Our understanding of the molecular control of morphological processes has increased tremendously over recent years through the development and use of high resolution in vivo imaging approaches, which have enabled cell behaviour to be linked to molecular functions. Here we review how such approaches have furthered our understanding of tracheal branching morphogenesis in Drosophila, during which the control of cell invagination, migration, competition and rearrangement is accompanied by the sequential secretion and resorption of proteins into the apical luminal space, a vital step in the elaboration of the trachea's complex tubular network. We also discuss the similarities and differences between flies and vertebrates in branched organ formation that are becoming apparent from these studies. IntroductionBranching morphogenesis restructures epithelial sheets to give rise to organs of fascinating three-dimensional architecture, as exemplified by the adult lung, the kidney and the vasculature in humans. In Drosophila melanogaster, genetic studies have provided much insight into the regulatory networks that regulate the ordered formation of tracheal branches in the embryo, and into how the different branches coordinate their relative sizes, an issue that is of importance to the physical aspects of branched organ function (Affolter et al., 2003;Ghabrial et al., 2003;Uv et al., 2003). More recently, the development of live-imaging approaches in Drosophila have allowed researchers to take a deeper look at the behaviour of cells during the branching process, and have enabled events at the molecular level to be linked to the behaviour of individual cells or groups of cells.This combination of molecular genetics and live-imaging techniques has provided investigators with a unique opportunity to understand the morphological processes that occur during branching morphogenesis. This review focuses and builds on some of these recent insights, and assesses how they have led to a better understanding of the cellular and molecular processes that contribute to the transformation of simple, two-dimensional epithelial sheets into fascinating, three-dimensional tubular structures that can perform important functions in development and homeostasis. We focus here on the Drosophila tracheal system because several cellular and molecular paradigms, such as cell migration, competition and rearrangement, as well as the elaboration of a complex apical luminal environment, have recently been uncovered in this system that might serve related roles in the formation of other branched organs or tissues; these similarities might help us in the future to gain an even better understanding of how morphogenesis in general is regulated during development. Tracheal development in the fly embryoThe complex structure of the tracheal system consists of interconnected, metameric units of different-sized tubes that extend over the entire embryo shortly before hatching (Samakovlis et al., 1996b) (see Fig. 1, see also Movie 1 in the supplementary material)....

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Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons

Cited by 106 publications

References 54 publications

Inhibition of medulloblastoma cell invasion by Slit

Inhibition of medulloblastoma cell invasion by Slit

Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion

Tracheal branching morphogenesis inDrosophila: new insights into cell behaviour and organ architecture

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